Update on Biomarkers of Chronic Inflammatory Processes Underlying Diabetic Neuropathy.

There is an increasing prevalence of diabetes mellitus (DM), particularly type 2 DM (T2DM), and its associated complications. T2DM is linked to insulin resistance, chronic inflammation, and oxidative stress, which can lead to both macrovascular and microvascular complications, including peripheral diabetic neuropathy (PDN). Inflammatory processes play a key role in the development and progression of T2DM and its complications, with specific markers like C-reactive protein (CRP), interleukins (ILs), and tumor necrosis factor (TNF)-α being associated with increased risk. Other key inflammatory markers such as nuclear factor kappa B (NF-κB) are activated under hyperglycemic and oxidative stress conditions and contribute to the aggravation of PDN by regulating inflammatory gene expression and enhancing endothelial dysfunction. Other important roles in the inflammatory processes are played by Toll-like receptors (TLRs), caveolin 1 (CAV1), and monocyte chemoattractant protein 1 (MCP1). There is a relationship between vitamin D deficiency and PDN, highlighting the critical role of vitamin D in regulating inflammation and immune responses. The involvement of macrophages in PDN is also suspected, emphasizing their role in chronic inflammation and nerve damage in diabetic patients. Vitamin D supplementation has been found to reduce neuropathy severity, decrease inflammatory markers, and improve glycemic control. These findings suggest that addressing vitamin D deficiency could offer therapeutic benefits for PDN. These molecular pathways are critical in understanding the pathogenesis of DM complications and may offer potential biomarkers or therapeutic targets including anti-inflammatory treatments, vitamin D supplementation, macrophage phenotype modulation, and lifestyle modifications, aimed at reducing inflammation and preventing PDN. Ongoing and more extensive clinical trials with the aim of investigating anti-inflammatory agents, TNF-α inhibitors, and antioxidants are needed to advance deeper into the understanding and treatment of painful diabetic neuropathy.

Sequential Surgical Correction of Macrodactyly: A Case Report and Literature Review.

This report discusses the case of a young female patient diagnosed with macrodactyly of the toes, a condition that significantly affected her daily life. From the age of three to 11, she underwent treatment due to the severe impact of her deformity, particularly on her ability to move comfortably and wear suitable footwear. The patient's macrodactyly presented a complex clinical challenge, necessitating multiple surgical procedures to manage it effectively. These surgeries included soft tissue reduction to decrease the bulk of the enlarged digits, epiphysiodesis to halt the growth of the affected bones, and amputations to address the disproportionate enlargement of the toes. Each surgical intervention was aimed at improving both the function and appearance of the affected foot, with a focus on enhancing the patient's mobility and comfort. Despite the difficulties associated with recovery, the patient showed significant improvements in her ability to walk and in the aesthetic appearance of her foot. This case underscores the importance of developing individualized treatment plans that consider the unique needs of each patient and setting realistic expectations for outcomes. It also highlights that, while surgical interventions can lead to functional and cosmetic benefits, the extent of these improvements may be limited due to the inherent complexities of macrodactyly. The case calls attention to the need for ongoing research and the accumulation of clinical experience to refine treatment approaches for macrodactyly. Such advancements are crucial for optimizing therapeutic outcomes and improving the quality of life for patients affected by this rare condition.

Cardiovascular Effects of Herbal Products and Their Interaction with Antihypertensive Drugs-Comprehensive Review.

Hypertension is a highly prevalent population-level disease that represents an important risk factor for several cardiovascular complications and occupies a leading position in mortality statistics. Antihypertensive therapy includes a wide variety of drugs. Additionally, the potential antihypertensive and cardioprotective effects of several phytotherapy products have been evaluated, as these could also be a valuable therapeutic option for the prevention, improvement or treatment of hypertension and its complications. The present review includes an evaluation of the cardioprotective and antihypertensive effects of garlic, Aloe vera, green tea, Ginkgo biloba, berberine, ginseng, Nigella sativa, Apium graveolens, thyme, cinnamon and ginger, and their possible interactions with antihypertensive drugs. A literature search was undertaken via the PubMed, Google Scholar, Embase and Cochrane databases. Research articles, systematic reviews and meta-analyses published between 2010 and 2023, in the English, Hungarian, and Romanian languages were selected.

Novel Strategy in the Detection of Adverse Cutaneous Drug Reactions: A Case Series Study.

With multimorbidity on the rise, adverse cutaneous drug reactions are becoming a daily challenge in clinical practice. The objective evaluation of the skin lesion is crucial but hardly realized due to missing technology and guidelines. In this study, the novel Dermus SkinScanner-U, an optically guided high-frequency ultrasound imaging device, was evaluated regarding its comparability with the Dermatology Life Quality Index (DLQI) and the pharmacological analysis of the patients' drug therapy. A total of 40 adult patients were evaluated, all with chronic medication use and skin lesions that led to non-compliance toward the pharmacotherapy. With the ongoing aim of further improving the methodology, the first results, with two detailed patient cases, are presented here. It was concluded that in the cases evaluated, there was a significant correlation between the characteristics of the lesions observed on the optical and ultrasound image, the DLQI score, and the pharmacological analysis. The next steps include increasing the scale of the study to ultimately develop a quality-assured methodology for the correct diagnosis of skin-related adverse drug reactions and to prepare a database with the most frequently observed events.

Finite Element Analysis of Various Osteotomies Used in the Treatment of Developmental Hip Dysplasia in Children.

Late-discovered developmental hip dysplasia deformities often necessitate complex surgical treatments and meticulous preoperative planning. The selection of osteotomies is contingent upon the patient's age and the specific structural deformity of the hip. In our anatomical hip model, derived from the data of a 12-year-old patient, we performed virtual osteotomies that are commonly recommended for such cases. We precisely constructed geometric models for various osteotomies, including the Dega, Pemberton, Tönnis, Ganz, Chiari pelvic, and Pauwels femoral osteotomies. We employed Autodesk Inventor for the finite element analysis of the hip joint and the corrective osteotomies. In comparing one-stage osteotomies, we noted that the Dega and Ganz pelvic osteotomies, especially when combined with the Pauwels femoral osteotomy, yielded the most favorable outcomes. These combinations led to enhanced femoral head coverage and reduced intra-articular pressure. Furthermore, we calculated the femoral head-to-acetabulum volume ratio for both the Dega and Pauwels osteotomies. The encouraging results we obtained advocate for the integration of finite element analysis in virtual osteotomies of the pelvis and femur as a preoperative tool in the management of developmental hip dysplasia.

Finite Element Analysis of Normal and Dysplastic Hip Joints in Children.

From a surgical point of view, quantification cannot always be achieved in the developmental deformity in hip joints, but finite element analysis can be a helpful tool to compare normal joint architecture with a dysplastic counterpart. CT scans from the normal right hip of an 8-year-old boy and the dysplastic left hip of a 12-year-old girl were used to construct our geometric models. In a three-dimensional model construction, distinctions were made between the cortical bone, trabecular bone, cartilage, and contact nonlinearities of the hip joint. The mathematical model incorporated the consideration of the linear elastic and isotropic properties of bony tissue in children, separately for the cortical bone, trabecular bone, and articular cartilage. Hexahedral elements were used in Autodesk Inventor software version 2022 ("Ren") for finite element analysis of the two hips in the boundary conditions of the single-leg stance. In the normal hip joint on the cartilaginous surfaces of the acetabulum, we found a kidney-shaped stress distribution in a 471,672 mm2 area. The measured contact pressure values were between 3.0 and 4.3 MPa. In the dysplastic pediatric hip joint on a patch of 205,272 mm2 contact area, the contact pressure values reached 8.5 MPa. Furthermore, the acetabulum/femur head volume ratio was 20% higher in the dysplastic hip joint. We believe that the knowledge gained from the normal and dysplastic pediatric hip joints can be used to develop surgical treatment methods and quantify and compare the efficiency of different surgical treatments used in children with hip dysplasia.

Assessment of vitamin B12 levels and cardiovascular risk factors in metformin- and non-metformin-treated type 2 diabetic patients.

Oxidative stress enhances cardiovascular risk. Metformin decreases intestinal absorption of vitamin B12. Our objective was the evaluation of type 2 diabetics focusing on differences due to their treatment. A prospective study on 224 type 2 diabetics was realized between 2015-2018 in Targu Mures, Romania, divided into 2 subgroups (metformin vs. other therapy - 2nd/3rd generation sulfonylureas, insulin, dietary regimen -, followed for at least one year) and non-diabetic controls (n=25) for oxidative stress level comparison. Serum homocysteine (HC), vitamin B12 were determined by chemiluminescence (Immulite One). Lipid peroxidation was assessed by serum malondialdehyde (MDA) measurement (HPLC). Biochemical tests, minerals, cystatin C, high-sensitivity C reactive protein (hs-CRP) were measured on Konelab20Xti, glycated hemoglobin on Nycocard Reader. GraphPad InStat-3 was used for statistics. Negative correlation occured between serum vitamin B12 and HC, this vitamin's level was significantly lower and serum zinc was significantly higher in patients on metformin. Hyperhomocysteinemia was present in 87% of the subjects, 46% had zinc deficiency and 41% elevated hs-CRP. Serum cystatin C showed positive correlation with creatinine. Serum MDA was significantly higher in diabetics compared to control patients. Elevated hs-CRP and homocysteine represent raised cardiovascular risk. Intense oxidative stress, vitamin, mineral deficiencies are frequent in diabetic subjects.

The Management of COVID-19-Related Coagulopathy: A Focus on the Challenges of Metabolic and Vascular Diseases.

The course of COVID-19 is highly dependent on the associated cardiometabolic comorbidities of the patient, which worsen the prognosis of coronavirus infection, mainly due to systemic inflammation, endothelium dysfunction, and thrombosis. A search on the recent medical literature was performed in five languages, using the PubMed, Embase, Cochrane, and Google Scholar databases, for the review of data regarding the management of patients with a high risk for severe COVID-19, focusing on the associated coagulopathy. Special features of COVID-19 management are presented, based on the underlying conditions (obesity, diabetes mellitus, and cardiovascular diseases), emphasizing the necessity of a modern, holistic approach to thromboembolic states. The latest findings regarding the most efficient therapeutic approaches are included in the article, offering guidance for medical professionals in severe, complicated cases of SARS-CoV-2 infection. We can conclude that severe COVID-19 is closely related to vascular inflammation and intense cytokine release leading to hemostasis disorders. Overweight, hyperglycemia, cardiovascular diseases, and old age are important risk factors for severe outcomes of coronavirus infection, involving a hypercoagulable state. Early diagnosis and proper therapy in complicated SARS-CoV-2-infected cases could reduce mortality and the need for intensive care during hospitalization in patients with cardiometabolic comorbidities.

The Approach of Artificial Intelligence in Neuroendocrine Carcinomas of the Breast: A Next Step towards Precision Pathology?-A Case Report and Review of the Literature.

Primary neuroendocrine tumors (NETs) of the breast are considered a rare and undervalued subtype of breast carcinoma that occur mainly in postmenopausal women and are graded as G1 or G2 NETs or an invasive neuroendocrine carcinoma (NEC) (small cell or large cell). To establish a final diagnosis of breast carcinoma with neuroendocrine differentiation, it is essential to perform an immunohistochemical profile of the tumor, using antibodies against synaptophysin or chromogranin, as well as the MIB-1 proliferation index, one of the most controversial markers in breast pathology regarding its methodology in current clinical practice. A standardization error between institutions and pathologists regarding the evaluation of the MIB-1 proliferation index is present. Another challenge refers to the counting process of MIB-1's expressiveness, which is known as a time-consuming process. The involvement of AI (artificial intelligence) automated systems could be a solution for diagnosing early stages, as well. We present the case of a post-menopausal 79-year-old woman diagnosed with primary neuroendocrine carcinoma of the breast (NECB). The purpose of this paper is to expose the interpretation of MIB-1 expression in our patient' s case of breast neuroendocrine carcinoma, assisted by artificial intelligence (AI) software (HALO-IndicaLabs), and to analyze the associations between MIB-1 and common histopathological parameters.

Pathways of Coagulopathy and Inflammatory Response in SARS-CoV-2 Infection among Type 2 Diabetic Patients.

Chronic inflammation and endothelium dysfunction are present in diabetic patients. COVID-19 has a high mortality rate in association with diabetes, partially due to the development of thromboembolic events in the context of coronavirus infection. The purpose of this review is to present the most important underlying pathomechanisms in the development of COVID-19-related coagulopathy in diabetic patients. The methodology consisted of data collection and synthesis from the recent scientific literature by accessing different databases (Cochrane, PubMed, Embase). The main results are the comprehensive and detailed presentation of the very complex interrelations between different factors and pathways involved in the development of arteriopathy and thrombosis in COVID-19-infected diabetic patients. Several genetic and metabolic factors influence the course of COVID-19 within the background of diabetes mellitus. Extensive knowledge of the underlying pathomechanisms of SARS-CoV-2-related vasculopathy and coagulopathy in diabetic subjects contributes to a better understanding of the manifestations in this highly vulnerable group of patients; thus, they can benefit from a modern, more efficient approach regarding diagnostic and therapeutic management.

Relationship between Nutrition, Lifestyle Habits and Laboratory Parameters in Hypertensive Patients with/without Cognitive Dysfunction.

(1) Background: Cognitive dysfunction is a major concern in hypertensive patients. Lifestyle habits and nutrition influence laboratory parameters, with an impact on clinical course. The objective of the study was to evaluate nutrition and lifestyle habits in hypertensive patients with/without cognitive dysfunction and establish correlations to laboratory parameters. MATERIAL AND METHODS: 50 patients admitted to the Cardiovascular Rehabilitation Clinic in Târgu Mureș were enrolled in this study between March-June 2021. We evaluated their cognitive function, and they filled in a questionnaire about lifestyle and nutrition. Biochemical blood tests were performed using a Konelab Prime 60i analyzer. IBM-SPSS22 and GraphPad InStat3 were used for statistics. RESULTS: Mean age of hypertensive patients (n = 50) was 70.42 ± 4.82 (SD) years, half of them had cognitive dysfunction. Zinc deficiency was present in 74% of the subjects. The subgroup with cognitive dysfunction had significantly higher BMI (p = 0.009) and microalbuminuria (p = 0.0479), as well as significantly lower magnesium intake (p = 0.032) and cholesterol intake (p = 0.022), compared to those with normal cognitive status. CONCLUSIONS: Nutrition is in a close relationship with laboratory parameters; significant differences (microalbuminuria, cholesterol intake, BMI, etc.) are present between hypertensive patients with/without cognitive dysfunction. A healthy diet is important for the maintenance of metabolic balance, the achievement of optimal body weight, and the prevention of complications.

Diagnosis and Management of Dysgerminomas with a Brief Summary of Primitive Germ Cell Tumors.

Dysgerminoma represents a rare malignant tumor composed of germ cells, originally from the embryonic gonads. Regarding its incidence, we do not have precise data due to its rarity. Dysgerminoma occurs at a fertile age. The preferred treatment is the surgical removal of the tumor succeeded by the preservation of fertility. Even if a multidisciplinary team, founded in 2009 by a gynecologist, an oncologist, a pediatric oncologist and a pediatric surgeon, under the guidance of the Malignant Germ Cell International Consortium (MaGIC), studies this type of tumor, issues still remain related to the lack of a randomized study and to both the management and understanding of the concept of OMGCTs (ovarian malignant germ cell tumors). The aim of this review is to present from the literature the various approaches for this type of tumor, and, regarding innovative therapies or possible prevention, which can be applied in clinical practice. Multidisciplinarity and treatment in reference centers have proven their usefulness as well.

Oxidative stress and peripartum outcomes (Review).

Pregnancy, labor and childbirth are accompanied by excessive oxidative aggression. The excessive formation of free radicals [reactive oxygen species (ROS), reactive nitrogen species (RNS), chlorine reactive species (CRS)] causes cellular oxidative damage, which can be scavenged by enzymatic or non-enzymatic antioxidants in normal healthy pregnancy, physiological labor and delivery without any complications. An imbalance between the pro-oxidant and antioxidant factors may lead to oxidative stress, which contributes to the development of many diseases. This oxidative aggression can be a precursor for pathologies in the pregnant woman including eclampsia, miscarriage, preterm labor, and intrauterine growth retardation; in the offspring it may lead to bronchopulmonary dysplasia/chronic lung disease, necrotizing enterocolitis, retinopathy of prematurity, and periventricular leukomalacia. This review summarizes the studies conducted to identify the mechanisms of oxidative stress and the effect of cell membrane oxidation, the mechanisms that are behind oxidative stress-related diseases, and also those studies which have demonstrated the effect of antioxidants in preventing diseases or diminishing the effects of oxidative stress in the body, in obstetrics and neonatology.